Associations between Antiepileptic Use and Hypogammaglobulinaemia: Findings from a Population-Based Case-Control Study Using Data Linkage.

BACKGROUND AND OBJECTIVES: Increased mortality in epilepsy due to infections (other than pneumonia) has been demonstrated. Small case series of people on antiepileptic drugs (AEDs) have described hypogammaglobulinaemia, which may predispose to infections. It is unclear whether hypogammaglobulinaemia is more frequent in people on AEDs, what AEDs it is associated with, or what clinical impact it has. In this population-based study, we aimed to determine whether AEDs were associated with hypogammaglobulinaemia, which AEDs were associated, and whether the associations may be causal. METHODS: We conducted an unmatched case-control study using data linkage of routinely collected biochemistry, prescribing, and morbidity datasets in North-East Scotland from 2009-2021. Cases were participants with immunoglobulin levels less than the reference range. Controls were those with normal/high immunoglobulin levels. Logistic regression was used to investigate associations between AED exposure and any hypogammaglobulinaemia, adjusting for age, sex, and comorbidity. We also analysed low IgA, IgM, and IgG separately. We analysed "any AED" exposure and common individual drugs separately. Cumulative exposure data were used to determine whether an exposure-response relationship was present. RESULTS: 18,666 cases and 127,157 controls were identified. Use of any AED was associated with increased risk of hypogammaglobulinaemia (adjusted odds ratio [aOR] 1.20 [95% CI: 1.15-1.25]). Phenytoin use was strongly associated with low IgA (aOR 5.90 [95% CI: 3.04, 10.43]). Carbamazepine and lamotrigine were also associated with low IgA. Apart from topiramate, which was associated with a non-significant decrease in odds of hypogammaglobulinaemia, there was a consistent increase in odds of hypogammaglobulinaemia across most AEDs studied. Panhypogammaglobulinaemia was associated with any AED use, carbamazepine, lamotrigine, gabapentin, and multiple AED use. There was evidence of an exposure-response relationship between any AED use and any hypogammaglobulinaemia, low IgA, and low IgG. Carbamazepine and probably lamotrigine also had an exposure-response relationship with any hypogammaglobulinaemia. DISCUSSION: AEDs may increase hypogammaglobulinaemia risk. Specific classes of immunoglobulins are differentially affected, and the exposure-response analysis suggests this may be causal. Further work should investigate the clinical impact of these findings. Clinicians should check immunoglobulin levels if unusual or recurrent infections occur in patients treated with AEDs.

Calcaneal broadband ultrasound attenuation predicts physical capability: EPIC-Norfolk prospective population-based study.

BACKGROUND: Calcaneal ultrasound (broadband ultrasound attenuation - BUA), a marker of bone strength, may predict future physical capability and thus provide a strategy to identify individuals at risk of age-related deterioration of health. This study aims to determine if BUA can predict future physical capability among middle-aged and older adults. METHODS: Summary performance scores (SPS), an objective quantification of physical capability, were devised using participants' measures of standing balance, gait speed and timed chair rises. Associations between BUA and SPS, measured at least six years apart, were investigated using univariable and multivariate sex-specific linear and logistic regression, adjusting for confounders. RESULTS: 5893 participants were included. In men and women, for every five points lower BUA, there was a 0.2-point decrease in SPS. In women, BUA less than one standard deviation below the mean was associated with low physical capability (defined as SPS 3-6); fully adjusted odds ratio (OR) (95 % confidence interval (CI)) 1.35 (1.01-1.84). No association existed among men; OR (95 % CI) 0.84 (0.59-1.19). Significant risk factors for low physical capability in men with baseline low BUA were: older age [OR 5.77]; high BMI [OR 2.85]; lower social class [OR 1.59]; low physical activity [OR 1.64]. Risk factors among women were: older age [OR 5.54]; high BMI [OR 2.08]; lower education [OR 1.42], low physical activity [OR 1.27]; steroid use [OR 2.05]; and stroke [OR 2.74]. CONCLUSION: BUA may predict future physical capability in older adults. With further validation, BUA could stratify individuals at risk of deterioration in physical health.

First delirium episode in Parkinson's disease and parkinsonism: incidence, predictors, and outcomes.

To define the incidence, predictors and prognosis of the first hospital delirium episode in Parkinson's disease (PD) and atypical parkinsonism (AP), we identified the first hospital episode of delirium after diagnosis in the Parkinsonism Incidence in North-East Scotland (PINE) study, a prospective community-based incidence cohort of parkinsonism, using chart-based criteria to define delirium. Of 296 patients (189=PD, 107=AP [dementia with Lewy bodies, progressive supranuclear palsy, multiple system atrophy, vascular parkinsonism]), 152 developed delirium (PD = 98, AP = 54). Incidence of first hospital delirium episode per 100 person years was 8.1 (95% confidence interval [CI] 6.6-9.9) in PD and 18.5 (95% CI 13.9-24.7) in AP. Independent predictors of delirium were atypical parkinsonism (Hazard ratio [HR] vs PD = 2.83 [95% CI 1.60-5.03], age in PD but not in AP (HR for 10-year increase 2.29 [95% CI 1.74-3.02]), baseline MMSE (HR = 0.94 [95% CI 0.89-0.99]), APOE ε4 in PD (HR 2.16 [95% CI 1.15-4.08]), and MAPT H1/H1 in PD (HR 2.08 [95% CI 1.08-4.00]). Hazards of dementia and death after delirium vs before delirium were increased (dementia: HR = 6.93 [95% CI 4.18-11.48] in parkinsonism; death: HR = 3.76 [95% CI 2.65-5.35] in PD, 1.59 [95% CI 1.04-2.42] in AP). Delirium is a common non-motor feature of PD and AP and is associated with increased hazards of dementia and mortality. Whether interventions for early identification and treatment improve outcomes requires investigation.